What is the appropriate next step for a patient with a non-positive varicella (chickenpox) vaccine titer after a second dose, and can immunity be confirmed after a potential third dose?

Varicella Vaccine Non-Response After Two Doses

A third dose of varicella vaccine is reasonable for healthcare personnel who remain seronegative after two properly-spaced doses, and you can document immunity based on vaccination history alone rather than serologic testing, as commercial assays lack sensitivity to detect vaccine-induced immunity and routine post-vaccination testing is not recommended. 1

Why Serologic Non-Response Occurs

Commercial antibody assays are the primary problem, not vaccine failure:

• Commercial ELISA and latex agglutination tests were designed to detect the higher antibody titers from natural infection, not the lower titers induced by vaccination 1, 2
• These assays lack sufficient sensitivity to detect vaccine-induced immunity in all cases, frequently yielding false-negative results even in protected individuals 1, 2
• Sensitive research assays (gpELISA and FAMA) demonstrate that 99% of adults develop antibodies after the second dose, but these tests are not commercially available 1
• Some vaccinated individuals produce adequate cell-mediated immunity and low-avidity antibodies that provide protection but fall below commercial assay detection thresholds 2, 3

True vaccine non-response is uncommon:

• Approximately 11.9% of healthcare workers remain seronegative by commercial assay after two doses, but this largely reflects assay limitations rather than true vaccine failure 3
• Among those who appear seronegative, many have adequate cell-mediated immunity and remain protected from clinical disease 2

Evidence of Immunity for Healthcare Personnel

The ACIP guidelines explicitly define acceptable evidence of immunity without requiring serologic confirmation:

Healthcare personnel are considered immune with any of the following 1:

• Written documentation of 2 doses of varicella vaccine (no titer required)
• Laboratory evidence of immunity or laboratory confirmation of disease
• Healthcare provider diagnosis or verification of varicella history
• Healthcare provider diagnosis or verification of herpes zoster history

Routine serologic testing after vaccination is not recommended for management of vaccinated healthcare personnel because available commercial assays cannot reliably detect vaccine-induced immunity 1

Approach to the Third Dose

A third dose is a reasonable strategy for persistently seronegative healthcare workers:

• Among healthcare workers who were seronegative after two doses, 7 of 7 (100%) seroconverted after a third dose by commercial assay 3
• However, 42.9% of these third-dose recipients still produced only low-avidity antibodies, suggesting the issue remains assay sensitivity rather than true non-response 3
• The third dose provides additional antigenic exposure and may boost both humoral and cell-mediated responses 3

Writing the Immunity Documentation

You can confidently document immunity after three doses based on vaccination history alone:

For your documentation, state:

• "This healthcare worker has received three doses of varicella vaccine (dates: ___). Per ACIP guidelines, written documentation of vaccination constitutes acceptable evidence of immunity for healthcare personnel, and routine post-vaccination serologic testing is not recommended due to insufficient sensitivity of commercial assays to detect vaccine-induced immunity." 1

Do not require further serologic testing because:

• Commercial assays will likely remain negative or equivocal despite adequate protection 1, 2
• The patient has demonstrated appropriate vaccination response through lack of clinical disease despite exposures 2
• ACIP explicitly accepts vaccination documentation as evidence of immunity without serologic confirmation 1

Management After Exposure

For vaccinated healthcare personnel exposed to varicella:

• Monitor daily during days 10-21 post-exposure for fever, skin lesions, and systemic symptoms 1
• Healthcare workers should report any symptoms immediately and be placed on sick leave if symptoms develop 1
• The risk of clinical disease after three doses is extremely low, even with negative commercial serology 2, 3

Critical Pitfall to Avoid

Do not continue repeated serologic testing or additional vaccine doses beyond three - this creates unnecessary anxiety, expense, and potential adverse events without improving protection. The issue is assay sensitivity, not vaccine failure. Three documented doses provide sufficient evidence of immunity for occupational health clearance. 1, 2